A growing proportion of children and adults take medication regularly, yet relatively few drugs have undergone adequate post-marketing surveillance for adverse effects, including elevated cancer rates. The main objective of this study is to identify drugs that are associated with lower or higher rates of cancer and examine whether these associations deserve further study. The proposed research builds on a drug surveillance program conducted within the Kaiser Permanente health plan over the last 30 years. Specifically, we propose to: 1) Continue surveillance of the 200 most commonly used prescription drugs for possible carcinogenic effects will be conducted among the entire KPMCP membership, about 3 million persons, starting, in part, in 1991. Cancer incidence among users of specific medications or groups of medications will be compared with those expected, based on rates in entire KPMCP membership. 2) Conduct pilot case-control studies of selected drug-cancer associations found in the above screening analyses will be conducted to determine whether the associations are likely due to confounding and, if not, whether there is evidence of a dose-response effect, or evidence against biological plausibility. The Kaiser Permanente membership and databases provide a unique resource for studying potential drug-cancer associations. The membership is large (3.1 million), stable, ethnically diverse, and receives virtually all of its health care from the pre-paid, integrated medical care program. Each year approximately 20 million prescriptions are dispensed to health plan members. The proposed research will provide a valuable mechanism to identify early signs of possible carcinogenic effects of the most commonly used medications or reassurance as to their safety in this regard.